{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T19:13:52Z","timestamp":1773774832580,"version":"3.50.1"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>In addition to having a sensory component, tinnitus disorder might also be involved in tinnitus-related distress, cognitive dysfunction, and\/or autonomic arousal, resulting in different behavioral changes and functional disabilities. The response to interventions has been shown to be heterogeneous in patients with tinnitus disorder. The underlying neural mechanisms of the heterogeneity of tinnitus disorder and their response to interventions remain elusive. Frailty and tinnitus share similar risk factors, including genetics; personality; early experience, aging and psychosocial stress; aging-related chronic systemic inflammation; vascular damage; neurodegenerative pathology; and functional decline in physical, cognitive, and psychosocial dimensions. The mechanisms by which frailty is linked to tinnitus disorder involve dysfunction of the HAP axis, cognitive and emotional processing, autonomic reactivity, and immune and metabolic regulation. Moreover, tinnitus, as a stressor, results in increased allostatic load, maladaptation, and adverse outcomes in individuals with frailty. The maladaptation induced by frailty contributes to the heterogeneity of tinnitus disorder, and the response to intervention is the synchronization of intrinsic brain networks characterized by increased integration and decreased segregation. Frailty may be associated with tinnitus chronification and relapse after effective intervention. We propose a model hypothesis to explain the bidirectional relationship between frailty and tinnitus disorder. In this model, the dysfunction of dynamic executive functioning might be the common pathway of tinnitus disorder and frailty. Investigating the efficacy of interventions for older people with frailty and tinnitus disorder will provide evidence about their benefits and disadvantages. Further exploration of vulnerability-related cortical and subcortical biomarkers of frailty and tinnitus disorder could provide guidance for the understanding and personalized prevention of tinnitus disorder.<\/jats:p>","DOI":"10.3389\/fneur.2025.1617821","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T04:10:44Z","timestamp":1754971844000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Frailty links the heterogeneity of tinnitus disorder and response to interventions in older patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Jian","family":"Ruan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwei","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijun","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.pbr.2020.12.002","article-title":"Tinnitus and tinnitus disorder: Theoretical and operational definitions (an international multidisciplinary proposal)","volume":"260","author":"De Ridder","year":"2021","journal-title":"Prog Brain Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/7854_2020_215","article-title":"Neurobiology of stress-induced tinnitus","volume":"51","author":"Szczepek","year":"2021","journal-title":"Curr Top Behav Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1001\/jamaneurol.2022.2189","article-title":"Global prevalence and incidence of tinnitus: a systematic review and meta-analysis","volume":"79","author":"Jarach","year":"2022","journal-title":"JAMA Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4320","DOI":"10.3390\/nu14204320","article-title":"Systems medicine approach for tinnitus with comorbid disorders","volume":"14","author":"Mazurek","year":"2022","journal-title":"Nutrients"},{"key":"B5","doi-asserted-by":"publisher","first-page":"583","DOI":"10.3390\/brainsci13040583","article-title":"The comorbidity of depression and anxiety symptoms in tinnitus sufferers: a network analysis","volume":"13","author":"Chen","year":"2023","journal-title":"Brain Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"836842","DOI":"10.3389\/fneur.2022.836842","article-title":"Increased risk of major depressive disorder following tinnitus: a population-based study","volume":"13","author":"Lin","year":"2022","journal-title":"Front Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.3390\/jcm12031169","article-title":"Tinnitus and its relation to depression, anxiety, and stress-a population-based cohort study","volume":"12","author":"Hackenberg","year":"2023","journal-title":"J Clin Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.3390\/brainsci12020275","article-title":"Dimensions of tinnitus-related distress","volume":"12","author":"Brueggemann","year":"2022","journal-title":"Brain Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1131979","DOI":"10.3389\/fnagi.2023.1131979","article-title":"The association between stress, emotional states, and tinnitus: a mini-review","volume":"15","author":"Patil","year":"2023","journal-title":"Front Aging Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.heares.2015.08.014","article-title":"Tinnitus and anxiety disorders: a review","volume":"333","author":"Pattyn","year":"2016","journal-title":"Hear Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e197","DOI":"10.1055\/s-0041-1735455","article-title":"Effect of tinnitus on sleep quality and insomnia","volume":"27","author":"Gallo","year":"2023","journal-title":"Int Arch Otorhinolaryngol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"101405","DOI":"10.1016\/j.smrv.2020.101405","article-title":"Effects of cognitive behavioural therapy on insomnia in adults with tinnitus: Systematic review and meta-analysis of randomised controlled trials","volume":"56","author":"Curtis","year":"2021","journal-title":"Sleep Med Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"113493","DOI":"10.1016\/j.bbr.2021.113493","article-title":"On the impairment of executive control of attention in chronic tinnitus: evidence from the attention network test","volume":"414","author":"Jensen","year":"2021","journal-title":"Behav Brain Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1080\/14992027.2016.1185168","article-title":"The impact of tinnitus upon cognition in adults: a systematic review","volume":"55","author":"Tegg-Quinn","year":"2016","journal-title":"Int J Audiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.3390\/jcm10091881","article-title":"Tinnitus and neuropsychological dysfunction in the elderly: a systematic review on possible links","volume":"10","author":"Malesci","year":"2021","journal-title":"J Clin Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jad.2022.11.009","article-title":"Tinnitus and risk of attempted suicide: a one year follow-up study","volume":"322","author":"Cheng","year":"2023","journal-title":"J Affect Disord."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1017\/S0022215121003066","article-title":"Suicidal ideation in people with tinnitus: a systematic review and meta-analysis","volume":"135","author":"Tailor","year":"2021","journal-title":"J Laryngol Otol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1002\/lary.26107","article-title":"Relationships between tinnitus and the prevalence of anxiety and depression","volume":"127","author":"Bhatt","year":"2017","journal-title":"Laryn Goscope."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e37733","DOI":"10.1371\/journal.pone.0037733","article-title":"Tinnitus severity is reduced with reduction of depressive mood\u2014a prospective population study in Sweden","volume":"7","author":"Hebert","year":"2012","journal-title":"PLoS ONE."},{"key":"B20","doi-asserted-by":"publisher","first-page":"341","DOI":"10.4088\/JCP.10m06176blu","article-title":"Comorbidity patterns of anxiety and depressive disorders in a large cohort study: The Netherlands Study of Depression and Anxiety (NESDA)","volume":"72","author":"Lamers","year":"2011","journal-title":"J Clin Psychiatry."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e041290","DOI":"10.1136\/bmjopen-2020-041290","article-title":"Natural history of tinnitus in adults: a cross-sectional and longitudinal analysis","volume":"10","author":"Dawes","year":"2020","journal-title":"BMJ Open."},{"key":"B22","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3389\/fnagi.2019.00053","article-title":"Editorial: towards an understanding of tinnitus heterogeneity","volume":"11","author":"Cederroth","year":"2019","journal-title":"Front Aging Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"196","DOI":"10.3389\/fneur.2014.00196","article-title":"A scientific cognitive-behavioral model of tinnitus: novel conceptualizations of tinnitus distress","volume":"5","author":"McKenna","year":"2014","journal-title":"Front Neurol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1046095","DOI":"10.3389\/fnins.2022.1046095","article-title":"Vulnerability to chronic stress and the phenotypic heterogeneity of presbycusis with subjective tinnitus","volume":"16","author":"Ruan","year":"2022","journal-title":"Front Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e02074","DOI":"10.1002\/brb3.2074","article-title":"The evaluation of global cognitive and emotional status of older patients with chronic tinnitus","volume":"11","author":"Fetoni","year":"2021","journal-title":"Brain Behav."},{"key":"B26","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1111\/psyg.12889","article-title":"Association between age-related hearing loss with tinnitus and cognitive performance in older community-dwelling Chinese adults","volume":"22","author":"Zhang","year":"2022","journal-title":"Psychogeriatrics."},{"key":"B27","doi-asserted-by":"publisher","first-page":"617610","DOI":"10.3389\/fpsyg.2020.617610","article-title":"Heterogeneous influence of frailty phenotypes in age-related hearing loss and tinnitus in chinese older adults: an explorative study","volume":"11","author":"Ruan","year":"2021","journal-title":"Front Psychol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/nrneurol.2016.12","article-title":"Maladaptive plasticity in tinnitus\u2013triggers, mechanisms and treatment","volume":"12","author":"Shore","year":"2016","journal-title":"Nat Rev Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"866","DOI":"10.3389\/fnins.2018.00866","article-title":"Pathophysiology of subjective tinnitus: triggers and maintenance","volume":"12","author":"Haider","year":"2018","journal-title":"Front Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/0168-0102(90)90031-9","article-title":"Phantom auditory perception (tinnitus): mechanisms of generation and perception","volume":"8","author":"Jastreboff","year":"1990","journal-title":"Neurosci Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.heares.2015.09.010","article-title":"Neural networks of tinnitus in humans: elucidating severity and habituation","volume":"334","author":"Husain","year":"2016","journal-title":"Hear Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3389\/fnsys.2012.00047","article-title":"Stress and tinnitus-from bedside to bench and back","volume":"6","author":"Mazurek","year":"2012","journal-title":"Front Syst Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.neubiorev.2013.03.021","article-title":"An integrative model of auditory phantom perception: tinnitus as a unified percept of interacting separable subnetworks","volume":"44","author":"De Ridder","year":"2014","journal-title":"Neurosci Biobehav Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s10162-018-00709-9","article-title":"Towards a mechanistic-driven precision medicine approach for tinnitus","volume":"20","author":"Tzounopoulos","year":"2019","journal-title":"J Assoc Res Otolaryngol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fneur.2015.00124","article-title":"Thalamocortical dysrhythmia: a theoretical update in tinnitus","volume":"6","author":"De Ridder","year":"2015","journal-title":"Front Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/S0140-6736(19)31786-6","article-title":"Frailty: implications for clinical practice and public health","volume":"394","author":"Hoogendijk","year":"2019","journal-title":"Lancet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1056\/NEJMra2301292","article-title":"Frailty in older adults","volume":"391","author":"Kim","year":"2024","journal-title":"N Engl J Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1093\/ageing\/afaa219","article-title":"Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population level studies","volume":"50","author":"O'Caoimh","year":"2021","journal-title":"Age Ageing."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.arr.2014.12.004","article-title":"Cognitive frailty, a novel target for the prevention of elderly dependency","volume":"20","author":"Ruan","year":"2015","journal-title":"Ageing Res Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.jamda.2017.02.004","article-title":"Association of social frailty with both cognitive and physical deficits among older people","volume":"18","author":"Tsutsumimoto","year":"2017","journal-title":"J Am Med Dir Assoc."},{"key":"B41","doi-asserted-by":"publisher","first-page":"879","DOI":"10.3233\/JAD-230312","article-title":"Depressive and biopsychosocial frailty phenotypes: impact on late-life cognitive disorders","volume":"94","author":"Panza","year":"2023","journal-title":"J Alzheimers Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1111\/joim.13384","article-title":"Associations between nutritional frailty and 8-year all-cause mortality in older adults: the Salus in Apulia Study","volume":"290","author":"Zupo","year":"2021","journal-title":"J Intern Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1136\/jech-2015-205789","article-title":"Intelligence and socioeconomic position in childhood in relation to frailty and cumulative allostatic load in later life: the Lothian Birth Cohort 1936","volume":"70","author":"Gale","year":"2016","journal-title":"J Epidemiol Community Health."},{"key":"B44","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1177\/1099800408323452","article-title":"Allostatic load and frailty in the women's health and aging studies","volume":"10","author":"Szanton","year":"2009","journal-title":"Biol Res Nurs."},{"key":"B45","doi-asserted-by":"publisher","first-page":"751022","DOI":"10.3389\/fmed.2021.751022","article-title":"Physiological dysregulation, frailty, and impacts on adverse health and functional outcomes","volume":"8","author":"Lu","year":"2021","journal-title":"Front Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.jpain.2012.04.003","article-title":"Role of allostatic load in sociodemographic patterns of pain prevalence in the US population","volume":"13","author":"Slade","year":"2012","journal-title":"J Pain"},{"key":"B47","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1097\/PSY.0000000000000281","article-title":"Allostatic load and personality: a 4-year longitudinal study","volume":"78","author":"Stephan","year":"2016","journal-title":"Psychosom Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.physbeh.2011.02.027","article-title":"Allostatic load associations to acute, 3-year and 6-year prospective depressive symptoms in healthy older adults","volume":"104","author":"Juster","year":"2011","journal-title":"Physiol Behav."},{"key":"B49","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/j.1365-2702.2008.02347.x","article-title":"Allostasis and allostatic load: expanding the discourse on stress and cardiovascular disease","volume":"17","author":"Logan","year":"2008","journal-title":"J Clin Nurs"},{"key":"B50","doi-asserted-by":"publisher","first-page":"100496","DOI":"10.1016\/j.bbih.2022.100496","article-title":"Allostatic load and risk of hearing impairment","volume":"25","author":"Matthews","year":"2022","journal-title":"Brain Behav Immun Health."},{"key":"B51","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1001\/jamaoto.2023.0948","article-title":"Hearing impairment and allostatic load in older adults","volume":"149","author":"Du","year":"2023","journal-title":"JAMA Otolaryngol Head Neck Surg."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1001\/jamaoto.2020.2920","article-title":"Novel risk loci in tinnitus and causal inference with neuropsychiatric disorders among adults of European ancestry","volume":"146","author":"Clifford","year":"2020","journal-title":"JAMA Otolaryngol Head Neck Surg."},{"key":"B53","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.heares.2012.08.015","article-title":"Associations between stress and hearing problems in humans","volume":"295","author":"Canlon","year":"2013","journal-title":"Hear Res."},{"key":"B54","first-page":"412","article-title":"Comorbidity of chronic tinnitus and psychological stress - which came first, the chicken or the egg?","volume":"32","author":"Pupi\u0107-Bakra\u010d","year":"2020","journal-title":"Psychiatr Danub."},{"key":"B55","doi-asserted-by":"publisher","first-page":"264","DOI":"10.2174\/1745017901814010264","article-title":"Tinnitus: the sound of stress?","volume":"14","author":"Ciminelli","year":"2018","journal-title":"Clin Pract Epidemiol Ment Health."},{"key":"B56","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s43587-021-00065-z","article-title":"Neural circuits and behavioral pathways linking hearing loss to affective dysregulation in older adults","volume":"1","author":"Brewster","year":"2021","journal-title":"Nat Aging."},{"key":"B57","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jpsychores.2013.08.018","article-title":"The prevalence of tinnitus and the relationship with neuroticism in a middle-aged UK population","volume":"76","author":"McCormack","year":"2014","journal-title":"J Psychosom Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e375","DOI":"10.1055\/s-0039-1688469","article-title":"Possible association between the lack of regular physical activity with tinnitus and headache: cross-sectional Study","volume":"23","author":"Bazoni","year":"2019","journal-title":"Int Arch Otorhinolaryngol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e59344","DOI":"10.7759\/cureus.59344","article-title":"The role of diet and lifestyle in the tinnitus management: a comprehensive review","volume":"16","author":"Wadhwa","year":"2024","journal-title":"Cureus."},{"key":"B60","doi-asserted-by":"publisher","first-page":"afad020","DOI":"10.1093\/ageing\/afad020","article-title":"New horizons in holistic, person-centred health promotion for hearing healthcare","volume":"52","author":"Maidment","year":"2023","journal-title":"Age Ageing"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1426609","DOI":"10.3389\/fmed.2024.1426609","article-title":"Association between hearing loss, tinnitus, and chronic kidney disease: the NHANES 2015-2018","volume":"11","author":"Zou","year":"2024","journal-title":"Front Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1001\/jamaoto.2023.0052","article-title":"Association of plasma metabolomic biomarkers with persistent tinnitus: a population-based case-control study","volume":"149","author":"Zeleznik","year":"2023","journal-title":"JAMA Otolaryngol Head Neck Surg."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5604\/01.3001.0014.7445","article-title":"Drug-induced diseases in otolaryngology - causes, clinical signs, treatment","volume":"75","author":"Woro\u0144","year":"2021","journal-title":"Otolaryngol Pol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"4033","DOI":"10.1121\/1.5132707","article-title":"The role of diet in vulnerability to noise-induced cochlear injury and hearing loss","volume":"146","author":"Spankovich","year":"2019","journal-title":"J Acoust Soc Am."},{"key":"B65","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1177\/00034894241242330","article-title":"Vitamin D deficiency as a risk factor of tinnitus: an epidemiological study","volume":"133","author":"Aliyeva","year":"2024","journal-title":"Ann Otol Rhinol Laryngol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"93","DOI":"10.4103\/1463-1741.178485","article-title":"Therapeutic role of Vitamin B12 in patients of chronic tinnitus: a pilot study","volume":"18","author":"Singh","year":"2016","journal-title":"Noise Health."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1038\/s43587-023-00504-z","article-title":"Navigating and diagnosing cognitive frailty in research and clinical domains","volume":"3","author":"Nader","year":"2023","journal-title":"Nat Aging."},{"key":"B68","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/S0140-6736(12)62167-9","article-title":"Frailty in elderly people","volume":"381","author":"Clegg","year":"2013","journal-title":"Lancet."},{"key":"B69","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/S0018-506X(02)00024-7","article-title":"The concept of allostasis in biology and biomedicine","volume":"43","author":"McEwen","year":"2003","journal-title":"Horm Behav."},{"key":"B70","first-page":"412","article-title":"Comorbidity of chronic tinnitus and psychological stress - which came first, the chicken or the egg?","volume":"32","author":"Pupi\u0107-Bakra\u010d","year":"2020","journal-title":"Psychiatr Danub."},{"key":"B71","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/bs.pbr.2021.01.022","article-title":"Evidence for biological markers of tinnitus: a systematic review","volume":"262","author":"Haider","year":"2021","journal-title":"Prog Brain Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3389\/fnagi.2018.00098","article-title":"Cholinergic hypofunction in presbycusis-related tinnitus with cognitive function impairment: emerging hypotheses","volume":"10","author":"Ruan","year":"2018","journal-title":"Front Aging Neurosci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.neulet.2006.10.028","article-title":"The sound of stress: blunted cortisol reactivity to psychosocial stress in tinnitus sufferers","volume":"411","author":"H\u00e9bert","year":"2007","journal-title":"Neurosci Lett."},{"key":"B74","doi-asserted-by":"publisher","first-page":"570196","DOI":"10.3389\/fpsyg.2020.570196","article-title":"Stress and tinnitus; transcutaneous auricular vagal nerve stimulation attenuates tinnitus-triggered stress reaction","volume":"11","author":"Ylikoski","year":"2020","journal-title":"Front Psychol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"883926","DOI":"10.3389\/fnbeh.2022.883926","article-title":"Higher peripheral inflammation is associated with lower orbitofrontal gamma power in chronic tinnitus","volume":"16","author":"Becker","year":"2022","journal-title":"Front Behav Neurosci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1080\/14992027.2019.1698775","article-title":"Tinnitus, hearing loss and inflammatory processes in an older Portuguese population","volume":"59","author":"Haider","year":"2020","journal-title":"Int J Audiol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.bjorl.2019.01.009","article-title":"Evaluation of serum prolidase enzyme activity and oxidative stress in patients with tinnitus","volume":"86","author":"Ekinci","year":"2020","journal-title":"Braz J Otorhinolaryngol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.cell.2010.10.002","article-title":"Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction","volume":"143","author":"Someya","year":"2010","journal-title":"Cell."},{"key":"B79","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.genhosppsych.2011.12.006","article-title":"Psychopathological dimensions of tinnitus and psychopharmacologic approaches in its treatment","volume":"34","author":"Belli","year":"2012","journal-title":"Gen Hosp Psychiatry."},{"key":"B80","volume-title":"Evidence Review for Combinations of Management Strategies: Tinnitus: Assessment and Management: Evidence Review P","year":"2020"},{"key":"B81","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3238\/arztebl.m2022.0135","article-title":"Chronic tinnitus","volume":"119","author":"Mazurek","year":"2022","journal-title":"Dtsch Arztebl Int."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1002\/lary.21851","article-title":"The effects of unilateral cochlear implantation on the tinnitus handicap inventory and the influence on quality of life","volume":"121","author":"Amoodi","year":"2011","journal-title":"Laryngoscope."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1001\/jama.2020.0697","article-title":"Tinnitus","volume":"323","author":"Piccirillo","year":"2020","journal-title":"JAMA."},{"key":"B84","volume-title":"Evidence Review for Psychological Therapies: Tinnitus: Assessment and Management: Evidence Review L","year":"2020"},{"key":"B85","doi-asserted-by":"publisher","first-page":"CD012614","DOI":"10.1002\/14651858.CD012614.pub2","article-title":"Cognitive behavioural therapy for tinnitus","volume":"1","author":"Fuller","year":"2020","journal-title":"Cochrane Database Syst Rev."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1001\/jamaoto.2018.2238","article-title":"Effectiveness of guided internet-based cognitive behavioral therapy vs face-to-face clinical care for treatment of tinnitus: a randomized clinical trial","volume":"144","author":"Beukes","year":"2018","journal-title":"JAMA Otolaryngol Head Neck Surg."},{"key":"B87","doi-asserted-by":"publisher","first-page":"e049384","DOI":"10.1136\/bmjopen-2021-049384","article-title":"Internet-based cognitive-behavioural therapy for tinnitus: secondary analysis to examine predictors of outcomes","volume":"11","author":"Rodrigo","year":"2021","journal-title":"BMJ Open."},{"key":"B88","doi-asserted-by":"publisher","first-page":"eadk3222","DOI":"10.1126\/sciadv.adk3222","article-title":"Different components of cognitive-behavioral therapy affect specific cognitive mechanisms","volume":"10","author":"Norbury","year":"2024","journal-title":"Sci Adv"},{"key":"B89","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1001\/jamaoto.2024.2264","article-title":"Predictors of response to cognitive behavioral therapy in patients with tinnitus","volume":"150","author":"Mueller","year":"2024","journal-title":"JAMA Otolaryngol Head Neck Surg."},{"key":"B90","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.brs.2010.11.003","article-title":"Transcranial magnetic stimulation for the treatment of tinnitus: 4-year follow-up in treatment responders\u2013a retrospective analysis","volume":"4","author":"Burger","year":"2011","journal-title":"Brain Stimul."},{"key":"B91","doi-asserted-by":"publisher","first-page":"103862","DOI":"10.1016\/j.ebiom.2022.103862","article-title":"Specific brain network predictors of interventions with different mechanisms for tinnitus patients","volume":"76","author":"Lan","year":"2022","journal-title":"EBioMedicine."},{"key":"B92","doi-asserted-by":"publisher","first-page":"e01652","DOI":"10.1002\/brb3.1652","article-title":"Alterations of local functional connectivity in lifespan: a resting-state fMRI study","volume":"10","author":"Wen","year":"2020","journal-title":"Brain Behav."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1038\/s43587-021-00125-4","article-title":"Long-term prognosis and educational determinants of brain network decline in older adult individuals","volume":"1","author":"Chan","year":"2021","journal-title":"Nat Aging."},{"key":"B94","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.neuroimage.2019.01.041","article-title":"Patterns of functional connectivity in an aging population: the Rotterdam Study","volume":"189","author":"Zonneveld","year":"2019","journal-title":"Neuroimage."},{"key":"B95","doi-asserted-by":"publisher","first-page":"15223","DOI":"10.1523\/JNEUROSCI.3252-09.2009","article-title":"One-year brain atrophy evident in healthy aging","volume":"29","author":"Fjell","year":"2009","journal-title":"J Neurosci."},{"key":"B96","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1093\/cercor\/bht212","article-title":"Reduced frontal cortex efficiency is associated with lower white matter integrity in aging","volume":"25","author":"Zhu","year":"2015","journal-title":"Cereb Cortex."},{"key":"B97","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1097\/MOO.0b013e3283577b81","article-title":"Tinnitus and underlying brain mechanisms","volume":"20","author":"Galazyuk","year":"2012","journal-title":"Curr Opin Otolaryngol Head Neck Surg."},{"key":"B98","doi-asserted-by":"publisher","first-page":"205","DOI":"10.21053\/ceo.2022.00815","article-title":"Tinnitus and the triple network model: a perspective","volume":"15","author":"De Ridder","year":"2022","journal-title":"Clin Exp Otorhinolaryngol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"9889","DOI":"10.3390\/ijms24129889","article-title":"Targeting the limbic system: insights into its involvement in tinnitus","volume":"24","author":"Singh","year":"2023","journal-title":"Int J Mol Sci."},{"key":"B100","doi-asserted-by":"publisher","first-page":"5338","DOI":"10.1523\/JNEUROSCI.4793-11.2012","article-title":"Pathways for emotions and attention converge on the thalamic reticular nucleus in primates","volume":"32","author":"Zikopoulos","year":"2012","journal-title":"J Neurosci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.cell.2014.06.025","article-title":"State dependent architecture of thalamic reticular subnetworks","volume":"158","author":"Halassa","year":"2014","journal-title":"Cell."},{"key":"B102","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.celrep.2019.06.050","article-title":"Projection from the amygdala to the thalamic reticular nucleus amplifies cortical sound responses","volume":"28","author":"Aizenberg","year":"2019","journal-title":"Cell Rep"},{"key":"B103","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainresrev.2004.04.008","article-title":"The thalamic reticular nucleus: Structure, function and concept","volume":"46","author":"Pinault","year":"2004","journal-title":"Brain Res Brain Res Rev."},{"key":"B104","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/bs.pbr.2020.07.012","article-title":"The Bayesian brain in imbalance: medial, lateral and descending pathways in tinnitus and pain: a perspective","volume":"262","author":"De Ridder","year":"2021","journal-title":"Prog Brain Res."},{"key":"B105","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3389\/fnsys.2012.00002","article-title":"van Dijk P. Tinnitus does not require macroscopic tonotopic map reorganization","volume":"6","author":"Langers","year":"2012","journal-title":"Front Syst Neurosci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3389\/fnsys.2012.00021","article-title":"Cortico-limbic morphology separates tinnitus from tinnitus distress","volume":"6","author":"Leaver","year":"2012","journal-title":"Front Syst Neurosci"},{"key":"B107","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.neuron.2010.12.002","article-title":"Dysregulation of limbic and auditory networks in tinnitus","volume":"69","author":"Leaver","year":"2011","journal-title":"Neuron."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1152\/jn.1985.54.6.1473","article-title":"Abolition of spindle oscillations in thalamic neurons disconnected from nucleus reticularis thalami","volume":"54","author":"Steriade","year":"1985","journal-title":"J Neurophysiol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fnsys.2012.00015","article-title":"Neuroimaging and neuromodulation: complementary approaches for identifying the neuronal correlates of tinnitus","volume":"6","author":"Langguth","year":"2012","journal-title":"Front Syst Neurosci."},{"key":"B110","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.nicl.2017.07.015","article-title":"Connectivity of precuneus to the default mode and dorsal attention networks: a possible invariant marker of long-term tinnitus","volume":"16","author":"Schmidt","year":"2017","journal-title":"Neuroimage Clin."},{"key":"B111","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.2147\/NDT.S164619","article-title":"Tinnitus distress is associated with enhanced resting-state functional connectivity within the default mode network","volume":"14","author":"Chen","year":"2018","journal-title":"Neuropsychiatr Dis Treat."},{"key":"B112","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.tins.2016.10.004","article-title":"An integrative tin nitus model based on sensory precision","volume":"39","author":"Sedley","year":"2016","journal-title":"Trends Neurosci."},{"key":"B113","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41380-021-01265-0","article-title":"Influ ences of dopaminergic system dysfunction on late-life depression","volume":"27","author":"Taylor","year":"2022","journal-title":"Mol Psy Chiatry."},{"key":"B114","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.dib.2018.10.044","article-title":"Functional connectivity analysis of fMRI data collected from human subjects with chronic tinnitus and varying levels of tinnitus-related distress","volume":"21","author":"Hullfish","year":"2018","journal-title":"Data Brief."},{"key":"B115","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.neurobiolaging.2018.06.032","article-title":"The association between brain volume, cortical brain infarcts, and physical frailty","volume":"70","author":"Kant","year":"2018","journal-title":"Neurobiol Aging."},{"key":"B116","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3389\/fmed.2018.00284","article-title":"Scoping review of neuroimaging studies investigating frailty and frailty components","volume":"5","author":"L\u00f3pez-Sanz","year":"2018","journal-title":"Front Med."},{"key":"B117","doi-asserted-by":"publisher","first-page":"546344","DOI":"10.3389\/fmed.2020.546344","article-title":"Microstructural neuroimaging of frailty in cognitively normal older adults","volume":"7","author":"Tian","year":"2020","journal-title":"Front Med."},{"key":"B118","doi-asserted-by":"publisher","first-page":"605","DOI":"10.3233\/JAD-190622","article-title":"Cross-sectional association between cognitive frailty and white matter hyperintensity among memory clinic patients","volume":"72","author":"Sugimoto","year":"2019","journal-title":"J Alzheimers Dis."},{"key":"B119","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1111\/ggi.12708","article-title":"Neuroimaging signatures of frailty: a population-based study in community-dwelling older adults (the Atahualpa Project)","volume":"17","author":"Del Brutto","year":"2017","journal-title":"Geriatr Gerontol Int."},{"key":"B120","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1523\/JNEUROSCI.0697-21.2021","article-title":"Neurophysiological and brain structural markers of cognitive frailty differ from Alzheimer's disease","volume":"42","author":"Kocagoncu","year":"2022","journal-title":"J Neurosci."},{"key":"B121","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3389\/fmed.2020.00322","article-title":"Functional connectivity disruption in frail older adults without global cognitive deficits","volume":"7","author":"Su\u00e1rez-M\u00e9ndez","year":"2020","journal-title":"Front Med."},{"key":"B122","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1093\/gerona\/glz297","article-title":"Functional connectivity of the supplementary motor network is associated with Fried's modified frailty score in older adults","volume":"75","author":"Lammers","year":"2020","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"B123","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2023.01.001","article-title":"Brain connectivity in frailty: Insights from The Irish Longitudinal Study on Ageing (TILDA)","volume":"124","author":"Z\u00fa\u00f1iga","year":"2023","journal-title":"Neurobiol Aging."},{"key":"B124","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1007\/s11357-022-00702-4","article-title":"Frailty and functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI): baseline results from the SYNERGIC trial","volume":"45","author":"Bray","year":"2023","journal-title":"Geroscience."},{"key":"B125","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.semcdb.2021.05.002","article-title":"Brain-based mechanisms of late-life depression: Implications for novel interventions","volume":"116","author":"Gunning","year":"2021","journal-title":"Semin Cell Dev Biol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41398-023-02464-9","article-title":"Biological factors influencing depression in later life: role of aging processes and treatment implications","volume":"13","author":"Szymkowicz","year":"2023","journal-title":"Transl Psychiatry."},{"key":"B127","doi-asserted-by":"publisher","first-page":"109","DOI":"10.31083\/j.jin2205109","article-title":"Which came first, age-related hearing loss with tinnitus or cognitive impairment? What are the potential pathways?","volume":"22","author":"Ruan","year":"2023","journal-title":"J Integr Neurosci."},{"key":"B128","doi-asserted-by":"publisher","first-page":"1458542","DOI":"10.3389\/fnagi.2024.1458542","article-title":"Association between frailty index and cognitive dysfunction in older adults: insights from the 2011-2014 NHANES data","volume":"16","author":"Zhou","year":"2024","journal-title":"Front Aging Neurosci."},{"key":"B129","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1186\/s40359-024-02007-x","article-title":"Independent and combined associations of depression and cognitive impairment with frailty in oldest-old adults","volume":"12","author":"Zhao","year":"2024","journal-title":"BMC Psychol."},{"key":"B130","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.3389\/fpsyg.2016.02067","article-title":"Balancing automatic-controlled behaviors and emotional-salience states: a dynamic executive functioning hypothesis","volume":"7","author":"Kluwe-Schiavon","year":"2017","journal-title":"Front Psychol."},{"key":"B131","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jpsychires.2021.03.039","article-title":"Is neuroticism differentially associated with risk of Alzheimer's disease, vascular dementia, and frontotemporal dementia?","volume":"138","author":"Terracciano","year":"2021","journal-title":"J Psychiatr Res."},{"key":"B132","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1007\/s11126-017-9502-2","article-title":"The role of questioning environment, personality traits, depressive and anxiety symptoms in tinnitus severity perception","volume":"88","author":"Strumila","year":"2017","journal-title":"Psychiatr Q."},{"key":"B133","doi-asserted-by":"publisher","first-page":"M158","DOI":"10.1093\/gerona\/56.3.M158","article-title":"Associations of subclinical cardiovascular disease with frailty","volume":"56","author":"Newman","year":"2001","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B134","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1093\/gerona\/glw347","article-title":"Vascular cerebral damage in frail older adults: the AMImage study","volume":"72","author":"Avila-Funes","year":"2017","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"B135","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1212\/WNL.0b013e318294b462","article-title":"Association of brain pathology with the progression of frailty in older adults","volume":"80","author":"Buchman","year":"2013","journal-title":"Neurology."},{"key":"B136","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/j.jad.2021.08.086","article-title":"Psychological risk factors and the course of depression and anxiety disorders: a review of 15 years NESDA research","volume":"295","author":"Struijs","year":"2021","journal-title":"J Affect Disord."},{"key":"B137","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/gps.4495","article-title":"Lone liness, depression and cognitive function in older US adults","volume":"32","author":"Donovan","year":"2017","journal-title":"Int J Geriatr Psychiatry"},{"key":"B138","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3109\/14992029509042204","article-title":"Psychological profile of help-seeking and non-help-seeking tinnitus patients","volume":"24","author":"Attias","year":"1995","journal-title":"Scand Audiol."},{"key":"B139","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/0022-3999(95)00512-9","article-title":"The relationship between locus of control, tinnitus severity, and emotional distress in a group of tinnitus sufferers","volume":"39","author":"Budd","year":"1995","journal-title":"J Psychosom Res."},{"key":"B140","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.pneurobio.2018.07.003","article-title":"Selective basal ganglia vulnerability to energy deprivation: experimental and clinical evidences","volume":"169","author":"Tambasco","year":"2018","journal-title":"Prog Neurobiol."},{"key":"B141","doi-asserted-by":"publisher","first-page":"273","DOI":"10.2147\/CIA.S509990","article-title":"The biological rationale for integrating intrinsic capacity into frailty models","volume":"20","author":"Yu","year":"2025","journal-title":"Clin Interv Aging."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1617821\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T04:10:46Z","timestamp":1754971846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1617821\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":141,"alternative-id":["10.3389\/fneur.2025.1617821"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1617821","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]},"article-number":"1617821"}}